1. Field of the Invention
The present invention relates to a therapeutic agent for ischemia, more specifically, to a therapeutic agent for ischemia which inhibits apoptosis under ischemic condition.
2. Description of the Prior Art
As the death rate from cardiovascular diseases is increasing recently, researches on the cardiovascular diseases are now in rapid progress. Among them, one of the most noticeable field is that relating to thrombus, wherein efforts to restore blood vessel functions by dissolving thrombus which is the major cause of blockage of blood vessels, and, furthermore, to inhibit thrombus formation are being made. However, there is little progress in developing method for preventing ripple effects of blockage of blood vessels caused by thrombus or other causes. Accordingly, in case of a patient dying of the blockage of blood vessels, it is almost impossible to alleviate ischemic injury which lacks an adequate supply of oxygen and glucose.
It has been reported that administration of antibiotics to the patient who has antibody against Chlamydia pneumoniae which is related to onset of acute myocardial infarction reduces the onset rate of acute myocardial infarction(see: Meier C. R. et al., JAMA, 281(5):427-431, 1999). Antibiotics such as quinolones or quinones could reduce onset rate of acute myocardial infarction, on the other hand, antibiotics of macrolide which are known to be the most effective agents to kill Chlamydia pneumoniae have no effect on reducing the onset rate of acute myocardial infarction, suggesting that the antibiotics are not merely killing pathogenic microorganisms. Thus, antibiotics have been regarded as thrombosis inhibitors or thrombolytic agents, however, there is no evidence of relations between antibiotics and thrombus, hence, antibiotics can be conjectured to work on acute myocardial infarction via other mechanism than involvement of thrombus. The fact that antibiotics exert a certain effect on acute myocardial infarction without involvement of thrombus implies that antibiotics may protect cells from destruction caused by inadequate supply of oxygen and glucose due to the blockage of blood vessels. Accordingly, it could be expected that the patient who has ischemia due to the blockage of blood vessel can be recovered by using antibiotics, however, there is still little progress in researches of this area.
Under the circumstances, there is a continuing need to understand the mechanism of inhibiting cell damage which is prelude to ischemia and to develop an agent effectively inhibiting the ischemic cell damage.
The present inventors have made an effort to elucidate the mechanism of inhibiting cell damage which is prelude to ischemia and to develop a therapeutic agent effectively inhibiting the said ischemic cell damage, and, based on the fact that the death of cells under hypoxic and hypoglycemic condition is progressed via apoptosis, they discovered that the addition of antibiotics of quinolones, quinones, aminoglycosides or chloramphenicol to the cells under hypoxic and hypoglycemic condition can dramatically inhibit apoptosis, furthermore, the apoptosis can be inhibited by administering the antibiotics to an individual under ischemic condition in an amount of administering to the individual infected with pathogenic microorganisms.
A primary object of the present invention is, therefore, to provide a therapeutic agent which inhibits apoptosis under ischemic condition.